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At least 829 records · Page 46

CSP Plant Optimization Study for the California Power Market (“CalCSP”) (Final Technical Report)

Concentrating Solar Power (CSP) with thermal energy storage offers a unique and strategic opportunity to support California’s clean energy transition. Unlike photovoltaic (PV) systems, CSP with thermal storage can generate electricity after sunset and during periods of high demand, making it a valuable complement to intermittent renewable resources. CSP also provides synchronous, inertia-contributing generation, long-duration storage, and flexible dispatch—capabilities increasingly important as thermal plants retire. This report summarizes the findings of the CSP Plant Optimization Study for the California Power Market or “CalCSP study,” which evaluated the technical, economic, environmental, and policy factors that influence the deployment of CSP technologies in California. The CalCSP study was conducted to assess how CSP can contribute to California’s long-term decarbonization goals while enhancing grid reliability, supporting local economic development, and making efficient use of land and transmission resources. It draws on detailed modeling of CSP performance and costs, site suitability analysis, policy reviews, and stakeholder engagement across utilities, regulators, developers, and community organizations. The analysis focuses on mature molten-salt tower technology and incorporates lessons learned from the global CSP fleet, distinguishing today’s CSP from earlier first-of-a-kind projects in the U.S. The findings support a more prominent role for CSP in California’s evolving clean energy landscape. With strategic planning, targeted policy support, and continued cost improvements, CSP can complement PV and batteries to deliver reliable, around-the-clock clean electricity—especially in areas with high solar resource and constrained grid capacity.

14 SOLAR ENERGY↗

Multidisciplinary Design Optimization (MDO) Methods: Their Synergy with Computer Technology in Design Process

The paper identifies speed, agility, human interface, generation of sensitivity information, task decomposition, and data transmission (including storage) as important attributes for a computer environment to have in order to support engineering design effectively. It is argued that when examined in terms of these attributes the presently available environment can be shown to be inadequate a radical improvement is needed, and it may be achieved by combining new methods that have recently emerged from multidisciplinary design optimization (MDO) with massively parallel processing computer technology. The caveat is that, for successful use of that technology in engineering computing, new paradigms for computing will have to be developed - specifically, innovative algorithms that are intrinsically parallel so that their performance scales up linearly with the number of processors. It may be speculated that the idea of simulating a complex behavior by interaction of a large number of very simple models may be an inspiration for the above algorithms, the cellular automata are an example. Because of the long lead time needed to develop and mature new paradigms, development should be now, even though the widespread availability of massively parallel processing is still a few years away.

Sobieszczanski-Sobieski, Jaroslaw↗

Water Vapor Winds and Their Application to Climate Change Studies

The retrieval of satellite-derived winds and moisture from geostationary water vapor imagery has matured to the point where it may be applied to better understanding longer term climate changes that were previously not possible using conventional measurements or model analysis in data-sparse regions. In this paper, upper-tropospheric circulation features and moisture transport covering ENSO periods are presented and discussed. Precursors and other detectable interannual climate change signals are analyzed and compared to model diagnosed features. Estimates of winds and humidity over data-rich regions are used to show the robustness of the data and its value over regions that have previously eluded measurement.

Jedlovec, Gary J.↗

Multidisciplinary Design Optimisation (MDO) Methods: Their Synergy with Computer Technology in the Design Process

The paper identifies speed, agility, human interface, generation of sensitivity information, task decomposition, and data transmission (including storage) as important attributes for a computer environment to have in order to support engineering design effectively. It is argued that when examined in terms of these attributes the presently available environment can be shown to be inadequate. A radical improvement is needed, and it may be achieved by combining new methods that have recently emerged from multidisciplinary design optimisation (MDO) with massively parallel processing computer technology. The caveat is that, for successful use of that technology in engineering computing, new paradigms for computing will have to be developed - specifically, innovative algorithms that are intrinsically parallel so that their performance scales up linearly with the number of processors. It may be speculated that the idea of simulating a complex behaviour by interaction of a large number of very simple models may be an inspiration for the above algorithms; the cellular automata are an example. Because of the long lead time needed to develop and mature new paradigms, development should begin now, even though the widespread availability of massively parallel processing is still a few years away.

Sobieszczanski-Sobieski, Jaroslaw↗

Low-Speed Investigation of Upper-Surface Leading-Edge Blowing on a High-Speed Civil Transport Configuration

The paper identifies speed, agility, human interface, generation of sensitivity information, task decomposition, and data transmission (including storage) as important attributes for a computer environment to have in order to support engineering design effectively. It is argued that when examined in terms of these attributes the presently available environment can be shown to be inadequate. A radical improvement is needed, and it may be achieved by combining new methods that have recently emerged from multidisciplinary design optimisation (MDO) with massively parallel processing computer technology. The caveat is that, for successful use of that technology in engineering computing, new paradigms for computing will have to be developed - specifically, innovative algorithms that are intrinsically parallel so that their performance scales up linearly with the number of processors. It may be speculated that the idea of simulating a complex behaviour by interaction of a large number of very simple models may be an inspiration for the above algorithms; the cellular automata are an example. Because of the long lead time needed to develop and mature new paradigms, development should begin now, even though the widespread availability of massively parallel processing is still a few years away.

Banks, Daniel W.↗

The Effect of Feeding Purified versus Chow Diet on Bone Changes Produced by Hindlimb Suspension of Female Rats

Spaceflight simulation studies use chow diets while spaceflight studies use a semi-purified &et. To determine whether the differences in these diets would affect the changes in unweighted bone, we compared the effects of purified vs chow diet on bone parameters, urinary calcium, plasma estradiol, and urinary corticosterone (CORT) in sexually mature female Sprague-Dawley rats. Rats fed purified AIN-93G or chow diet were kept ambulatory (AMB) or subjected to a spaceflight simulation model of unweighted hindlimbs (HLS) for 38 days. Body mass of treatment groups was similar although food intake and caloric density of the diets differed. Both HLS diet groups showed similar decreases in bone mineral content and mechanical strength in unweighted femurs compared to AMB (p<0.05). However, femur length was lower (p<0.05) in the chow-fed than AIN-93G fed groups. Urinary calcium excretion was greater in chow than AIN-93G fed rats, consistent with the higher level of calcium in the diet. Plasma estradiol was lower in HLS than in AMB fed AIN-93G, but similar in HLS and AMB chow fed groups. Femur mineral content was related to plasma estradiol (r(sup 2) =0.91, p<0.00l). Urinary CORT excretion was increased during initial HLS and elevated in HLS/chow-fed rats. Diets did not appear to affect the osteopenia induced by unweighting, but effects on bone growth, calcium excretion, plasma estradiol and urinary CORT do not support the view that these diets can by used interchangeably in bone studies.

Tou, Janet↗

Analysis of a Dynamic Multi-Track Airway Concept for Air Traffic Management

The Dynamic Multi-track Airways (DMA) Concept for Air Traffic Management (ATM) proposes a network of high-altitude airways constructed of multiple, closely spaced, parallel tracks designed to increase en-route capacity in high-demand airspace corridors. Segregated from non-airway operations, these multi-track airways establish high-priority traffic flow corridors along optimal routes between major terminal areas throughout the National Airspace System (NAS). Air traffic controllers transition aircraft equipped for DMA operations to DMA entry points, the aircraft use autonomous control of airspeed to fly the continuous-airspace airway and achieve an economic benefit, and controllers then transition the aircraft from the DMA exit to the terminal area. Aircraft authority within the DMA includes responsibility for spacing and/or separation from other DMA aircraft. The DMA controller is responsible for coordinating the entry and exit of traffic to and from the DMA and for traffic flow management (TFM), including adjusting DMA routing on a daily basis to account for predicted weather and wind patterns and re-routing DMAs in real time to accommodate unpredicted weather changes. However, the DMA controller is not responsible for monitoring the DMA for traffic separation. This report defines the mature state concept, explores its feasibility and performance, and identifies potential benefits. The report also discusses (a) an analysis of a single DMA, which was modeled within the NAS to assess capacity and determine the impact of a single DMA on regional sector loads and conflict potential; (b) a demand analysis, which was conducted to determine likely city-pair candidates for a nationwide DMA network and to determine the expected demand fraction; (c) two track configurations, which were modeled and analyzed for their operational characteristic; (d) software-prototype airborne capabilities developed for DMA operations research; (e) a feasibility analysis of key attributes in the concept design; (f) a near-term, transitional application of the DMA concept as a proving ground for new airborne technologies; and (g) conclusions. The analysis indicates that the operational feasibility of a national DMA network faces significant challenges, especially for interactions between DMAs and between DMA and non-DMA traffic. Provided these issues are resolved, sectors near DMAs could experience significant local capacity benefits.

Wing, David J.↗

Advanced Usage of Vehicle Sketch Pad for CFD-Based Conceptual Design

Conceptual design is the most fluid phase of aircraft design. It is important to be able to perform large scale design space exploration of candidate concepts that can achieve the design intent to avoid more costly configuration changes in later stages of design. This also means that conceptual design is highly dependent on the disciplinary analysis tools to capture the underlying physics accurately. The required level of analysis fidelity can vary greatly depending on the application. Vehicle Sketch Pad (VSP) allows the designer to easily construct aircraft concepts and make changes as the design matures. More recent development efforts have enabled VSP to bridge the gap to high-fidelity analysis disciplines such as computational fluid dynamics and structural modeling for finite element analysis. This paper focuses on the current state-of-the-art geometry modeling for the automated process of analysis and design of low-boom supersonic concepts using VSP and several capability-enhancing design tools.

Ordaz, Irian↗

Analysis of Alternative Architectures for Cargo Lunar Landers

NASA’s Human Landing System (HLS) program has been working with commercial partners to develop human-class lunar landers to return the first American woman and next American man to the lunar surface in the mid 2020’s. In an effort to expand human presence beyond low Earth orbit, NASA’s Artemis program aims to facilitate a sustainable, long-term human presence in cis-lunar space. A component of this will require significant infrastructure to be delivered to the lunar surface. Delivering this infrastructure will require a significant lander capability that has yet to be developed. A thorough understanding of cargo lunar lander architectures is required such that select alternatives can be identified that best support the Artemis program’s objective of sustainability. The goal of this study is to aid NASA and its partners in the understanding of the cargo lunar lander trades space, as well as identify potential robust alternatives. The results will support NASA as it moves forward with key activities such as requirements formulation, agency strategic planning, and potential cargo lunar lander procurements. The study builds off of recent work performed by the Human Landing System program’s Architecture and Systems Analysis group to encompass a broad trade space of cargo lunar lander architecture alternatives. The current trade space as depicted by the morphological matrix and mission graph in Fig. 1 and Fig. 2, respectively, includes key alternative options that have become highly relevant due to current HLS activities and include on-orbit refueling, active cryogenic fluid management, Earth orbit aggregation, and global lunar access. The authors believe that there is also a statistically relevant impact of lander-payload configuration on the primary structure of the vehicle that could greatly impact alternative selection. Because of this, several conceptual lander-payload configurations will be evaluated to determine the level of impact. The current set of conceptual configurations are shown in Fig. 3 and Fig. 4. To aid the conceptual evaluation of these configurations, a catalogue of notional payloads has been developed that represent a wide range of masses and volumes that are expected to be delivered in support of a sustained human lunar presence, including pressurized and unpressurized rovers, surface habitats, power systems, and other support infrastructure. In order to execute this study in a timely fashion, a similar approach to that utilized in a similar 2019 study focused on 2024 human lunar sorties will be employed [1]. The team utilized a novel architecture synthesis framework currently being developed by NASA/MSFC to evaluate over 600,000 lunar lander architectures over a two month time frame [2]. From this large data set, varying ground rules and assumptions were applied as filters to explore the trade space to identify alternatives which exhibited robustness, as measured by launch vehicle payload margin, to absorb the natural growth that occurs during design maturation. The set of Earth-Moon system Delta-Vs assumed from the 2019 study, shown in Fig. 5, will be repurposed to accelerate model formulation for this effort. Additionally, current efforts in collaboration with the Georgia Institute of Technology’s Aerospace System Design Lab will be integrated to provide probabilistic modeling of the cargo lunar lander architectures to aid in identifying robust design alternatives [3]. The approach will help minimize potential impacts due to large levels of uncertainty inherent to pre phase-A conceptual design. By leveraging these past and present studies and partnerships, a highly detailed set of data can be generated in a short time period to aid NASA in the coming years to support the goal of a sustained human lunar presence.

Architectures↗

Addressing Thermal Model Run Time Concerns of the Wide Field Infrared Survey Telescope using Astrophysics Focused Telescope Assets (WFIRST-AFTA)

The Wide Field Infrared Survey Telescope using Astrophysics Focused Telescope Assets (WFIRST-AFTA) utilizes an existing 2.4 m diameter Hubble sized telescope donated from elsewhere in the federal government for near-infrared sky surveys and Exoplanet searches to answer crucial questions about the universe and dark energy. The WFIRST design continues to increase in maturity, detail, and complexity with each design cycle leading to a Mission Concept Review and entrance to the Mission Formulation Phase. Each cycle has required a Structural-Thermal-Optical-Performance (STOP) analysis to ensure the design can meet the stringent pointing and stability requirements. As such, the models have also grown in size and complexity leading to increased model run time. This paper addresses efforts to reduce the run time while still maintaining sufficient accuracy for STOP analyses. A technique was developed to identify slews between observing orientations that were sufficiently different to warrant recalculation of the environmental fluxes to reduce the total number of radiation calculation points. The inclusion of a cryocooler fluid loop in the model also forced smaller time-steps than desired, which greatly increases the overall run time. The analysis of this fluid model required mitigation to drive the run time down by solving portions of the model at different time scales. Lastly, investigations were made into the impact of the removal of small radiation couplings on run time and accuracy. Use of these techniques allowed the models to produce meaningful results within reasonable run times to meet project schedule deadlines.

Thermal Analysis↗

Urban-scale Energy Modeling: Scaling Beyond Tax Assessor Data

In an attempt to attain building-specific characteristics for urban-scale building energy models, county-specific tax assessors’ data is often an initial data source. This data source can contain valuable information such as year built, area, height, HVAC type, and roof/wall descriptions.We will show examples of 2,000 fields from Hamilton County in Tennessee with examples of many fields which are not relevant to urban-scale building energy modeling, are incorrect compared to other data sources, and highlight some lessons learned working with such a data source.There are currently 3,142 counties in the United States, each with their own data format, field definitions, and data access policy. As urban-scale involves city-scale analysis potentially covering multiple counties and matures toward state- or nation-scale analysis, county-by-county approaches are not scalable. While there are efforts to unify these datasets, there is an increasing proliferation of data and algorithms that can cover wider areas and provide more accurate inputs for urban-scale models. This paper summarizes computer vision of imagery, cartographic layers, building type assessment, and model generation used to achieve scalable detection and analysis of buildings.

New, Joshua↗

Evaluation of Bogus Vortex Techniques with Four-Dimensional Variational Data Assimilation

The effectiveness of techniques for creating "bogus" vortices in numerical simulations of hurricanes is examined by using the Penn State/NCAR nonhydrostatic mesoscale model (MM5) and its adjoint system. A series of four-dimensional variational data assimilation (4-D VAR) experiments is conducted to generate an initial vortex for Hurricane Georges (1998) in the Atlantic Ocean by assimilating bogus sea-level pressure and surface wind information into the mesoscale numerical model. Several different strategies are tested for improving the vortex representation. The initial vortices produced by the 4-D VAR technique are able to reproduce many of the structural features of mature hurricanes. The vortices also result in significant improvements to the hurricane forecasts in terms of both intensity and track. In particular, with assimilation of only bogus sea-level pressure information, the response in the wind field is contained largely within the divergent component, with strong convergence leading to strong upward motion near the center. Although the intensity of the initial vortex seems to be well represented, a dramatic spin down of the storm occurs within the first 6 h of the forecast. With assimilation of bogus surface wind data only, an expected dominance of the rotational component of the wind field is generated, but the minimum pressure is adjusted inadequately compared to the actual hurricane minimum pressure. Only when both the bogus surface pressure and wind information are assimilated together does the model produce a vortex that represents the actual intensity of the hurricane and results in significant improvements to forecasts of both hurricane intensity and track.

Pu, Zhao-Xia↗

Automated Finite Element Modeling of Wing Structures for Shape Optimization

The displacement formulation of the finite element method is the most general and most widely used technique for structural analysis of airplane configurations. Modem structural synthesis techniques based on the finite element method have reached a certain maturity in recent years, and large airplane structures can now be optimized with respect to sizing type design variables for many load cases subject to a rich variety of constraints including stress, buckling, frequency, stiffness and aeroelastic constraints (Refs. 1-3). These structural synthesis capabilities use gradient based nonlinear programming techniques to search for improved designs. For these techniques to be practical a major improvement was required in computational cost of finite element analyses (needed repeatedly in the optimization process). Thus, associated with the progress in structural optimization, a new perspective of structural analysis has emerged, namely, structural analysis specialized for design optimization application, or.what is known as "design oriented structural analysis" (Ref. 4). This discipline includes approximation concepts and methods for obtaining behavior sensitivity information (Ref. 1), all needed to make the optimization of large structural systems (modeled by thousands of degrees of freedom and thousands of design variables) practical and cost effective.

Harvey, Michael Stephen↗

Climate Change Impact Uncertainties for Maize in Panama: Farm Information, Climate Projections, and Yield Sensitivities

We present results from a pilot project to characterize and bound multi-disciplinary uncertainties around the assessment of maize (Zea mays) production impacts using the CERES-Maize crop model in a climate-sensitive region with a variety of farming systems (Panama). Segunda coa (autumn) maize yield in Panama currently suffers occasionally from high water stress at the end of the growing season, however under future climate conditions warmer temperatures accelerate crop maturation and elevated CO (sub 2) concentrations improve water retention. This combination reduces end-of-season water stresses and eventually leads to small mean yield gains according to median projections, although accelerated maturation reduces yields in seasons with low water stresses. Calibrations of cultivar traits, soil profile, and fertilizer amounts are most important for representing baseline yields, however sensitivity to all management factors is reduced in an assessment of future yield changes (most dramatically for fertilizers), suggesting that yield changes may be more generalizable than absolute yields. Uncertainty around General Circulation Model (GCM)s' projected changes in rainfall gain in importance throughout the century, with yield changes strongly correlated with growing season rainfall totals. Climate changes are expected to be obscured by the large inter-annual variations in Panamanian climate that will continue to be the dominant influence on seasonal maize yield into the coming decades. The relatively high (A2) and low (B1) emissions scenarios show little difference in their impact on future maize yields until the end of the century. Uncertainties related to the sensitivity of CERES-Maize to carbon dioxide concentrations have a substantial influence on projected changes, and remain a significant obstacle to climate change impacts assessment. Finally, an investigation into the potential of simple statistical yield emulators based upon key climate variables characterizes the important uncertainties behind the selection of climate change metrics and their performance against more complex process-based crop model simulations, revealing a danger in relying only on long-term mean quantities for crop impact assessment.

Maize↗

Lipid droplets fusion in adipocyte differentiated 3T3-L1 cells: A Monte Carlo simulation

Several human worldwide diseases like obesity, type 2 diabetes, hepatic steatosis, atherosclerosis and other metabolic pathologies are related to the excessive accumulation of lipids in cells. Lipids accumulate in spherical cellular inclusions called lipid droplets (LDs) whose sizes range from fraction to one hundred of micrometers in adipocytes. It has been suggested that LDs can grow in size due to a fusion process by which a larger LD is obtained with spherical shape and volume equal to the sum of the progenitors’ ones. In this study, the size distribution of two populations of LDs was analyzed in immature and mature (5-days differentiated) 3T3-L1 adipocytes (first and second populations, respectively) after Oil Red O staining. A Monte Carlo simulation of interaction between LDs has been developed in order to quantify the size distribution and the number of fusion events needed to obtain the distribution of the second population size starting from the first one. Four models are presented here based on different kinds of interaction: a surface weighted interaction (R2 Model), a volume weighted interaction (R3 Model), a random interaction (Random model) and an interaction related to the place where the LDs are born (Nearest Model). The last two models mimic quite well the behavior found in the experimental data. This work represents a first step in developing numerical simulations of the LDs growth process. Due to the complex phenomena involving LDs (absorption, growth through additional neutral lipid deposition in existing droplets, de novo formation and catabolism) the study focuses on the fusion process. The results suggest that, to obtain the observed size distribution, a number of fusion events comparable with the number of LDs themselves is needed. Moreover the MC approach results a powerful tool for investigating the LDs growth process. Highlights: • We evaluated the role of the fusion process in the synthesis of the lipid droplets. • We compared the size distribution of the lipid droplets in immature and mature cells. • We used the Monte Carlo simulation approach, simulating 10 thousand of fusion events. • Four different interaction models between the lipid droplets were tested. • The best model which mimics the experimental measures was selected.

60 APPLIED LIFE SCIENCES↗

Statistical and Probabilistic Extensions to Ground Operations' Discrete Event Simulation Modeling

NASA's human exploration initiatives will invest in technologies, public/private partnerships, and infrastructure, paving the way for the expansion of human civilization into the solar system and beyond. As it is has been for the past half century, the Kennedy Space Center will be the embarkation point for humankind's journey into the cosmos. Functioning as a next generation space launch complex, Kennedy's launch pads, integration facilities, processing areas, launch and recovery ranges will bustle with the activities of the world's space transportation providers. In developing this complex, KSC teams work through the potential operational scenarios: conducting trade studies, planning and budgeting for expensive and limited resources, and simulating alternative operational schemes. Numerous tools, among them discrete event simulation (DES), were matured during the Constellation Program to conduct such analyses with the purpose of optimizing the launch complex for maximum efficiency, safety, and flexibility while minimizing life cycle costs. Discrete event simulation is a computer-based modeling technique for complex and dynamic systems where the state of the system changes at discrete points in time and whose inputs may include random variables. DES is used to assess timelines and throughput, and to support operability studies and contingency analyses. It is applicable to any space launch campaign and informs decision-makers of the effects of varying numbers of expensive resources and the impact of off nominal scenarios on measures of performance. In order to develop representative DES models, methods were adopted, exploited, or created to extend traditional uses of DES. The Delphi method was adopted and utilized for task duration estimation. DES software was exploited for probabilistic event variation. A roll-up process was used, which was developed to reuse models and model elements in other less - detailed models. The DES team continues to innovate and expand DES capabilities to address KSC's planning needs.

Trocine, Linda↗

Propagation method and planting density influence canopy developmental transition and biomass productivity in Miscanthus × giganteus

Understanding how establishment practices influence the mechanisms underlying Miscanthus × giganteus (miscanthus) productivity and canopy development is critical for optimizing management. Data was collected during the juvenile (2011–2013) and mature (2024) phases of a long-term field experiment established in Urbana, Illinois, to evaluate the effects of propagation method (plug propagation [PP] and rhizome propagation [RP]), planting density (1.0, 0.75, and 0.25 plants m⁻²), and nitrogen application (0 and 67 kg N ha⁻¹) on end-of-season biomass yield, tiller mass, tiller density, and tiller height. Linear regression models identified the dominant predictors of yield across stand ages and management regimes. Planting density, nitrogen (N) application, and propagation method significantly influenced early yield and canopy development. During the juvenile phase, biomass yield was driven by tiller density due to canopy expansion; in the mature phase, yield became driven by tiller mass. The PP plots produced higher tiller density than the RP plots, resulting in faster canopy closure and higher juvenile-phase yields. Rhizome-propagated (RP) plots produced lower tiller density, but individual tillers were 3.3–6.4 g tiller −1 heavier than PP tillers. After the canopy reached equilibrium, the PP and RP yields were similar because greater RP tiller mass compensated for its lower tiller density. Higher planting density resulted in greater yield and tiller density during the second year (2012), but this effect was absent from the third year (2013) onward. In the juvenile phase, N fertilization enhanced yield by 1.6–3.4 Mg ha −1 . Initiating fertilization in 2013 on unfertilized plots produced biomass similar to that in fertilized plots, suggesting yield recovery in the mature phase. These findings revealed that establishment strategies, including propagation method and planting density, influence juvenile miscanthus canopy development and productivity, transitioning from tiller-density- to mass-dominated yields, but not mature phase productivity.

09 BIOMASS FUELS↗

Lack of anti-tumor activity with the β-catenin expression inhibitor EZN-3892 in the C57BL/6J Min/+ model of intestinal carcinogenesis

Highlights: • Wnt/β-catenin signaling is aberrantly activated in most colorectal cancers. • Locked nucleic acid (LNA)-based antisense is a novel tool for cancer therapy. • β-Catenin inhibition was observed in mature intestinal tissue of LNA-treated mice. • Further investigation of Wnt/β-catenin targeted therapies is warranted. - Abstract: Background: Previously, we showed that short-term inhibition of β-catenin expression and reversal of aberrant β-catenin subcellular localization by the selective COX-2 inhibitor celecoxib is associated with adenoma regression in the C57BL/6J Min/+ mouse. Conversly, long-term administration resulted in tumor resistance, leading us to investigate alternative methods for selective β-catenin chemoprevention. In this study, we hypothesized that disruption of β-catenin expression by EZN-3892, a selective locked nucleic acid (LNA)-based β-catenin inhibitor, would counteract the tumorigenic effect of Apc loss in Min/+ adenomas while preserving normal intestinal function. Materials and methods: C57BL/6J Apc{sup +/+} wild-type (WT) and Min/+ mice were treated with the maximum tolerated dose (MTD) of EZN-3892 (30 mg/kg). Drug effect on tumor numbers, β-catenin protein expression, and nuclear β-catenin localization were determined. Results: Although the tumor phenotype and β-catenin nuclear localization in Min/+ mice did not change following drug administration, we observed a decrease in β-catenin expression levels in the mature intestinal tissue of treated Min/+ and WT mice, providing proof of principle regarding successful delivery of the LNA-based antisense vehicle. Higher doses of EZN-3892 resulted in fatal outcomes in Min/+ mice, likely due to β-catenin ablation in the intestinal tissue and loss of function. Conclusions: Our data support the critical role of Wnt/β-catenin signaling in maintaining intestinal homeostasis and highlight the challenges of effective drug delivery to target disease without permanent toxicity to normal cellular function.

60 APPLIED LIFE SCIENCES↗